1. Field of the Invention
This invention relates to nitrone compounds and their use as therapeutic agents for the treatment of inflammation-related conditions and neuropathic pain in mammals, including humans.
2. State of the Art
Arthritis and related inflammatory disease conditions occur in more than 100 different forms, including rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis and systemic lupus erythematosus (SLE). Most forms of arthritis are characterized by some type of chronic inflammation. For example, RA typically involves chronic inflammation of the lining of the joints and/or the internal organs. Such chronic inflammation generally causes pain and swelling in the joints of those afflicted and may result in damage to cartilage, bone, tendons, ligaments and the like, ultimately leading to deformity and disability.
Neuropathic pain is a category of chronic pain that has been widely studied. Neuropathic pain occurs when the peripheral and/or central nervous systems are sensitized following an injury to the peripheral system. This initial injury can occur from a wide variety of causes including traumatic physical injury, as well as systemic diseases such as diabetes, herpes zoster, AIDS/HIV, syphilis and various other autoimmune diseases.
Examples of pain syndromes of this class include post herpetic neuralgia, neuritis, temporomandibular disorder, myofascial pain, back pain, and pain induced by inflammatory conditions. Neuropathic pain may occur in all body regions. For example, it may originate from the dental region. It may originate in regions which have suffered burn injury which often leads to neuropathic hyperalgesia in the affected body area. Neuropathic pain can also arise from neuralgia which in its acute phase involves intraneural inflammation which can cause damage to primary afferent axons, this inducing neuropathic pain. Neuropathic pain may also be induced by diabetic conditions (diabetic neuropathy). Neuropathy of primary afferent axons in long nerves is found in diabetic patients. Nociceptor sensitization may ensue.
Accordingly, a need exists for novel classes of therapeutic compounds which effectively treat arthritis and other inflammation-related conditions without producing undesired side effects. In addition, a need exists to treat the pain associated with joint disease such as arthritis, and a need exists to treat neuropathic pain which may present in the presence and absence of arthritis, as well as conditions such as traumatic brain injury and acute spinal cord injury.